Stability of cadmium resistance and metallothionein levels in vitro and in vivo.

Cultured cells can be adapted to large concentrations of the toxic cadmium ion, apparently by induction of synthesis of the Cd-binding protein metallothionein (MT). One human epithelial line derived from normal skin (HE100) and one murine fibroblast line, derived from L cells (C1 1D100), were used to study the stability of Cd resistance, the MT levels following omission of Cd, and the inducibility of MT synthesis in cells on reexposure to Cd. In the murine cells there was no significant loss of resistance during a 4-week period either after cultivation in vitro or after growing the cells in nude mice. In the human cells a decrease (50%) in resistance was noted the first week after Cd omission. After removing Cd from the cells, a rapid decrease in MT content was demonstrated. After 3 weeks of cultivation only trace amounts were left in both cell lines. However, approximately 60% (HE100) and 80% (C1 1D100) of the previous levels were demonstrated after reexposure to maximum tolerable doses for 24 hr. The data indicate that the degree of stability of Cd resistance is dependent on the capacity in cells for an immediate de novo synthesis of large amounts of MT on reexposure to Cd. The animal experiments demonstrate that Cd resistance is maintained even after growing the cells in vivo.